Bordetella pertussis, the microorganism which causes the disease commonly known as whooping cough, produces several toxins (i.e., pertussis toxin (PT) and heat labile or dermonecratic toxin) which appear to play important roles in pathogenesis of the organism. PT in addition is a major protective antigen which is a promising candidate for the development of a new acellular pertussis vaccine. The current project concentrates on elucidating the mechanisms by which pertussis toxin interacts with cells and elicits its diverse pharmacologic actions. The initial event in the interaction of PT with cells appears to be a rapid and essentially irreversible binding of toxin to cells. Using the interaction of PT with fetuin as a model, studies have been conducted which demonstrate that PT interacts with the carbohydrate moieties present in fetuin. Similar carbohydrate structures are present on cell surfaces and in a variety of serum glycoproteins including IgE and other immunoglobulins. The significance of these observations relative to the intoxication of cells and to specific adjuvant effects exhibited by PT are under consideration. The mechanism of action of PT is the toxin catalyzed transfer of an ADP-ribose moiety from NAD to specific acceptor protein (Ni). (Ni) is a cell membrane protein, which couples hormone receptor interaction to modulation of adenylate cyclase. Most of the effects elicited by PT appear to be associated with the covalent modification of (Ni). PT has served as an effective probe in purification of the regulatory (Ni) component and in elucidating the molecular mechanisms by which (Ni) acts in modulation of adenylate cyclase by inhibitory effectors. It has been established that (Ni), in part, functions by changing the affinity of the hormone receptor for ligand, thus when cells are treated with PT high affinity of binding of ligand is eliminated. Additional studies are in progress attempting to define more clearly the role of (Ni).